Miguel Morales
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Affiliation(s):
Universidad Autónoma de Barcelona
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Areas of Interest:
Alzheimer, Spines, electrophysiology, PI3K
Biography & Research:
The main topic of my research was the study of synaptic plasticity, either structural or functional. Nevertheless, during the last five years I made a significant contribution to the characterization of a PI3K-Akt-dependent signalling pathway controlling synapse formation. In doing so I have generated several membrane permeable peptides with the ability to activate PI3K. Additionally, based on the peptide structure and after an in silico screening, my colleagues and I have identified several putative PI3K activators. To develop this project I have followed a multidisciplinary approach, employing electrophysiology, confocal time-lapse microscopy, cellular biology techniques and behavioural experiments. Our results indicate that the effects of PI3K activation over synaptic function follows a two-phase temporal profile: (1) an early (during the first 24 hours) functional change that increases the size of the field potential, lasting for five days, and (2) a later structural change that increases the number of synapses/spines, which starts 48 hours after PI3K activation. Relevant to the project, the changes correlate with improved contextual memory acquisition.
The loss of synaptic connections is an early step of Alzheimer's disease, constituting a prodromic symptom that precedes the clinic onset of Alzheimer's. Preventing this synaptic loss may help mitigate or even revert the progression of the disease. In this sense, I have previously demonstrated that PI3K activation can restore spine loss in a Tg2576 AD mouse model Therefore, my future research will be the development of new therapies for AD, based on the control of the PI3K signaling pathway.
